Showing papers by "Georgetown University published in 2010"

Democracy and dictatorship revisited

Abstract: We address the strengths and weaknesses of the main available measures of political regime and extend the dichotomous regime classification first introduced in Alvarez et al. (Stud. Comp. Int. Dev. 31(2):3–36, 1996). This extension focuses on how incumbents are removed from office. We argue that differences across regime measures must be taken seriously and that they should be evaluated in terms of whether they (1) serve to address important research questions, (2) can be interpreted meaningfully, and (3) are reproducible. We argue that existing measures of democracy are not interchangeable and that the choice of measure should be guided by its theoretical and empirical underpinnings. We show that the choice of regime measure matters by replicating studies published in leading journals.

Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: The sleep heart health study

Abstract: Background— Clinic-based observational studies in men have reported that obstructive sleep apnea is associated with an increased incidence of coronary heart disease. The objective of this study was to assess the relation of obstructive sleep apnea to incident coronary heart disease and heart failure in a general community sample of adult men and women. Methods and Results— A total of 1927 men and 2495 women ≥40 years of age and free of coronary heart disease and heart failure at the time of baseline polysomnography were followed up for a median of 8.7 years in this prospective longitudinal epidemiological study. After adjustment for multiple risk factors, obstructive sleep apnea was a significant predictor of incident coronary heart disease (myocardial infarction, revascularization procedure, or coronary heart disease death) only in men ≤70 years of age (adjusted hazard ratio 1.10 [95% confidence interval 1.00 to 1.21] per 10-unit increase in apnea-hypopnea index [AHI]) but not in older men or in women of...

Association of Risk-Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers With Cancer Risk and Mortality

Abstract: Context Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. Objective To estimate risk and mortality reduction stratified by mutation and prior cancer status. Design, Setting, and Participants Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009. Main Outcomes Measures Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality. Results No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer–specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer–specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]). Conclusions Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer–specific mortality, and ovarian cancer–specific mortality.

Obstructive Sleep Apnea–Hypopnea and Incident Stroke: the Sleep Heart Health Study

Abstract: Rationale: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. Objectives: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. Methods: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea–hypopnea index (OAHI) and outcome was incident ischemic stroke. Measurements and Main Results: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1–7.4). In the mild to moderate range (OAHI, 5–25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2–10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. Conclusions: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.

Bilingual education in the 21st century: a global perspective

Abstract: Bilingual education in the 21st century: a global perspective, by Ofelia Garcia with contributions by Hugo Baetens Beardsmore, Oxford, UK, Wiley-Blackwell, 2009, 496 pp., US$99.95 (hardback), ISBN ...

Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.

Abstract: We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.

A Flood of Opioids, a Rising Tide of Deaths

Abstract: Faced with an epidemic of drug abuse and overdose deaths, the FDA has proposed a Risk Evaluation and Mitigation Strategy for prescription opioid pain relievers, involving improved education for physicians and patients about risks associated with long-acting opioids.

Examining the Protective Effects of Mindfulness Training on Working Memory Capacity and Affective Experience

Abstract: We investigated the impact of mindfulness training (MT) on working memory capacity (WMC) and affective experience. WMC is used in managing cognitive demands and regulating emotions. Yet, persistent and intensive demands, such as those experienced during high-stress intervals, may deplete WMC and lead to cognitive failures and emotional disturbances. We hypothesized that MT may mitigate these deleterious effects by bolstering WMC. We recruited 2 military cohorts during the high-stress predeployment interval and provided MT to 1 (MT, n 31) but not the other group (military control group, MC, n 17). The MT group attended an 8-week MT course and logged the amount of out-of-class time spent practicing formal MT exercises. The operation span task was used to index WMC at 2 testing sessions before and after the MT course. Although WMC remained stable over time in civilians (n 12), it degraded in the MC group. In the MT group, WMC decreased over time in those with low MT practice time, but increased in those with high practice time. Higher MT practice time also corresponded to lower levels of negative affect and higher levels of positive affect (indexed by the Positive and Negative Affect Schedule). The relationship between practice time and negative, but not positive, affect was mediated by WMC, indicating that MT-related improvements in WMC may support some but not all of MT’s salutary effects. Nonetheless, these findings suggest that sufficient MT practice may protect against functional impairments associated with high-stress contexts.

Politicized Places: Explaining Where and When Immigrants Provoke Local Opposition

Abstract: In ethnic and racial terms, America is growing rapidly more diverse. Yet attempts to extend racial threat hypotheses to today's immigrants have generated inconsistent results. This article develops the politicized places hypothesis, an alternative that focuses on how national and local conditions interact to construe immigrants as threatening. Hostile political reactions to neighboring immigrants are most likely when communities undergo sudden influxes of immigrants and when salient national rhetoric reinforces the threat. Data from several sources, including twelve geocoded surveys from 1992 to 2009, provide consistent support for this approach. Time-series cross-sectional and panel data allow the analysis to exploit exogenous shifts in salient national issues such as the September 11 attacks, reducing the problem of residential self-selection and other threats to validity. The article also tests the hypothesis using new data on local anti-immigrant policies. By highlighting the interaction of local and national conditions, the politicized places hypothesis can explain both individual attitudes and local political outcomes.

A Method of Automated Nonparametric Content Analysis for Social Science

Abstract: The increasing availability of digitized text presents enormous opportunities for social scientists. Yet hand coding many blogs, speeches, government records, newspapers, or other sources of unstructured text is infeasible. Although computer scientists have methods for automated content analysis, most are optimized to classify individual documents, whereas social scientists instead want generalizations about the population of documents, such as the proportion in a given category. Unfortunately, even a method with a high percent of individual documents correctly classified can be hugely biased when estimating category proportions. By directly optimizing for this social science goal, we develop a method that gives approximately unbiased estimates of category proportions even when the optimal classifier performs poorly. We illustrate with diverse data sets, including the daily expressed opinions of thousands of people about the U.S. presidency. We also make available software that implements our methods and large corpora of text for further analysis.

Quantum simulation of frustrated Ising spins with trapped ions

Abstract: A network is termed 'frustrated' when competing interactions between nodes prevent each bond from being satisfied. Frustration in quantum networks can lead to massively entangled ground states. The authors study this process by performing a quantum simulation of a frustrated spin system using three trapped atomic ions, whose interactions are precisely controlled using optical forces. A network is frustrated when competing interactions between nodes prevent each bond from being satisfied. Frustration in quantum networks can lead to massively entangled ground states, as occurs in exotic materials such as quantum spin liquids and spin glasses. Here, a quantum simulation of a frustrated spin system is described, in which there are three trapped atomic ions whose interactions are controlled using optical forces. A network is frustrated when competing interactions between nodes prevent each bond from being satisfied. This compromise is central to the behaviour of many complex systems, from social1 and neural2 networks to protein folding3 and magnetism4,5. Frustrated networks have highly degenerate ground states, with excess entropy and disorder even at zero temperature. In the case of quantum networks, frustration can lead to massively entangled ground states, underpinning exotic materials such as quantum spin liquids and spin glasses6,7,8,9. Here we realize a quantum simulation of frustrated Ising spins in a system of three trapped atomic ions10,11,12, whose interactions are precisely controlled using optical forces13. We study the ground state of this system as it adiabatically evolves from a transverse polarized state, and observe that frustration induces extra degeneracy. We also measure the entanglement in the system, finding a link between frustration and ground-state entanglement. This experimental system can be scaled to simulate larger numbers of spins, the ground states of which (for frustrated interactions) cannot be simulated on a classical computer.

Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology

Abstract: A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors' genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients' own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy-a type of adoptive cell immunotherapy-has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation's support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal research investment to accelerate the discovery of the next generation of cancer treatments. Another major trend in this year's report is progress in precision medicine approaches to treat cancer. Although precision medicine offers promise to people with cancer and their families, that promise is only as good as our ability to make these treatments available to all patients. My presidential theme, "Delivering Discoveries: Expanding the Reach of Precision Medicine," focuses on tackling this formidable challenge so that new targeted therapies are accessible to anyone who faces a cancer diagnosis. By improving access to high-quality care, harnessing big data on patient outcomes from across the globe, and pursuing innovative clinical trials, I am optimistic that we will speed the delivery of these most promising treatments to more patients. Sincerely, Bruce E. Johnson, FASCO ASCO President, 2017 to 2018.

Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study

Abstract: Summary Background Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT. Methods In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1. The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25. Study recruitment is closed; patient treatment and follow-up are ongoing. The study is registered with Clinical Trials.gov, NCT00396279. Findings Two patients had insufficient histology or radiology data for efficacy assessment. 30 of 35 (86%; 95% CI 70–95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology. Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4). Five patients had grade 3–5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related. Five serious adverse events were reported although none were deemed treatment related. Interpretation Further investigation of denosumab as a therapy for GCT is warranted. Funding Amgen, Inc.

A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

Abstract: We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

Genome sequences of the human body louse and its primary endosymbiont provide insights into the permanent parasitic lifestyle

Abstract: As an obligatory parasite of humans, the body louse (Pediculus humanus humanus) is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. Here, we present genome sequences of the body louse and its primary bacterial endosymbiont Candidatus Riesia pediculicola. The body louse has the smallest known insect genome, spanning 108 Mb. Despite its status as an obligate parasite, it retains a remarkably complete basal insect repertoire of 10,773 protein-coding genes and 57 microRNAs. Representing hemimetabolous insects, the genome of the body louse thus provides a reference for studies of holometabolous insects. Compared with other insect genomes, the body louse genome contains significantly fewer genes associated with environmental sensing and response, including odorant and gustatory receptors and detoxifying enzymes. The unique architecture of the 18 minicircular mitochondrial chromosomes of the body louse may be linked to the loss of the gene encoding the mitochondrial single-stranded DNA binding protein. The genome of the obligatory louse endosymbiont Candidatus Riesia pediculicola encodes less than 600 genes on a short, linear chromosome and a circular plasmid. The plasmid harbors a unique arrangement of genes required for the synthesis of pantothenate, an essential vitamin deficient in the louse diet. The human body louse, its primary endosymbiont, and the bacterial pathogens that it vectors all possess genomes reduced in size compared with their free-living close relatives. Thus, the body louse genome project offers unique information and tools to use in advancing understanding of coevolution among vectors, symbionts, and pathogens.

Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema

Abstract: BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

Abstract: We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

Respiratory morbidity in late preterm births

Abstract: Context Late preterm births (LPTB, 34 0/7-36 6/7 weeks) account for a growing proportion of prematurity-associated short term morbidities, particularly respiratory, that require specialized care and prolonged neonatal hospital stays.

Outcomes of Kidney Transplantation in HIV-Infected Recipients

Abstract: Background The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood. Methods We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy. Results Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90....

National Institutes of Health State-of-the-Science Conference Statement: Preventing Alzheimer Disease and Cognitive Decline

Abstract: The National Institute on Aging and the Office of Medical Applications of Research of the National Institutes of Health convened a State-of-the-Science Conference on 26-28 April 2010 to assess the available scientific evidence on prevention of cognitive decline and Alzheimer disease. This article provides the panel's assessment of the available evidence.

Age differences in affective decision making as indexed by performance on the Iowa Gambling Task.

Abstract: Contemporary perspectives on age differences in risk taking, informed by advances in developmental neuroscience, have emphasized the need to examine the ways in which emotional and cognitive factors interact to influence decision making. In the present study, a diverse sample of 901 individuals between the ages of 10 and 30 were administered a modified version of the Iowa Gambling Task, which is designed to measure affective decision making. Results indicate that approach behaviors (operationalized as the tendency to play increasingly from the advantageous decks over the course of the task) display an inverted U-shape relation to age, peaking in mid- to late adolescence. In contrast, avoidance behaviors (operationalized as the tendency to refrain from playing from the disadvantageous decks) increase linearly with age, with adults avoiding disadvantageous decks at higher rates than both preadolescents and adolescents. The finding that adolescents, compared to adults, are relatively more approach oriented in response to positive feedback and less avoidant in response to negative feedback is consistent with recent studies of brain development, as well as epidemiological data on various types of risky behavior, and may have important practical implications for the prevention of adolescent risk taking.

Emerging battery-ingestion hazard: clinical implications.

Abstract: OBJECTIVES: Recent cases suggest that severe and fatal button battery ingestions are increasing and current treatment may be inadequate. The objective of this study was to identify battery ingestion outcome predictors and trends, define the urgency of intervention, and refine treatment guidelines. METHODS: Data were analyzed from 3 sources: (1) National Poison Data System (56535 cases, 1985–2009); (2) National Battery Ingestion Hotline (8648 cases, July 1990–September 2008); and (3) medical literature and National Battery Ingestion Hotline cases (13 deaths and 73 major outcomes) involving esophageal or airway button battery lodgment. RESULTS: All 3 data sets signal worsening outcomes, with a 6.7-fold increase in the percentage of button battery ingestions with major or fatal outcomes from 1985 to 2009 (National Poison Data System). Ingestions of 20- to 25-mm-diameter cells increased from 1% to 18% of ingested button batteries (1990–2008), paralleling the rise in lithium-cell ingestions (1.3% to 24%). Outcomes were significantly worse for large-diameter lithium cells (≥20 mm) and children who were younger than 4 years. The 20-mm lithium cell was implicated in most severe outcomes. Severe burns with sequelae occurred in just 2 to 2.5 hours. Most fatal (92%) or major outcome (56%) ingestions were not witnessed. At least 27% of major outcome and 54% of fatal cases were misdiagnosed, usually because of nonspecific presentations. Injuries extended after removal, with unanticipated and delayed esophageal perforations, tracheoesophageal fistulas, fistulization into major vessels, and massive hemorrhage. CONCLUSIONS: Revised treatment guidelines promote expedited removal from the esophagus, increase vigilance for delayed complications, and identify patients who require urgent radiographs.

Hyponatremia-Induced Osteoporosis

Abstract: There is a high prevalence of chronic hyponatremia in the elderly, frequently owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Recent reports have shown that even mild hyponatremia is associated with impaired gait stability and increased falls. An increased risk of falls among elderly hyponatremic patients represents a risk factor for fractures, which would be further amplified if hyponatremia also contributed metabolically to bone loss. To evaluate this possibility, we studied a rat model of SIADH and analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). In rats, dual-energy X-ray absorptiometry (DXA) analysis of excised femurs established that hyponatremia for 3 months significantly reduced bone mineral density by approximately 30% compared with normonatremic control rats. Moreover, micro-computed tomography (µCT) and histomorphometric analyses indicated that hyponatremia markedly reduced both trabecular and cortical bone via increased bone resorption and decreased bone formation. Analysis of data from adults in NHANES III by linear regression models showed that mild hyponatremia is associated with increased odds of osteoporosis (T-score –2.5 or less) at the hip [odds ratio (OR) = 2.85; 95% confidence interval (CI) 1.03–7.86; p < .01]; all models were adjusted for age, sex, race, body mass index (BMI), physical activity, history of diuretic use, history of smoking, and serum 25-hydroxyvitamin D [25(OH)D] levels. Our results represent the first demonstration that chronic hyponatremia causes a substantial reduction of bone mass. Cross-sectional human data showing that hyponatremia is associated with significantly increased odds of osteoporosis are consistent with the experimental data in rodents. Our combined results suggest that bone quality should be assessed in all patients with chronic hyponatremia. © 2010 American Society for Bone and Mineral Research.

Cortical representation of natural complex sounds: effects of acoustic features and auditory object category.

Abstract: How the brain processes complex sounds, like voices or musical instrument sounds, is currently not well understood. The features comprising the acoustic profiles of such sounds are thought to be represented by neurons responding to increasing degrees of complexity throughout auditory cortex, with complete auditory "objects" encoded by neurons (or small networks of neurons) in anterior superior temporal regions. Although specialized voice and speech-sound regions have been proposed, it is unclear how other types of complex natural sounds are processed within this object-processing pathway. Using functional magnetic resonance imaging, we sought to demonstrate spatially distinct patterns of category-selective activity in human auditory cortex, independent of semantic content and low-level acoustic features. Category-selective responses were identified in anterior superior temporal regions, consisting of clusters selective for musical instrument sounds and for human speech. An additional subregion was identified that was particularly selective for the acoustic-phonetic content of speech. In contrast, regions along the superior temporal plane closer to primary auditory cortex were not selective for stimulus category, responding instead to specific acoustic features embedded in natural sounds, such as spectral structure and temporal modulation. Our results support a hierarchical organization of the anteroventral auditory-processing stream, with the most anterior regions representing the complete acoustic signature of auditory objects.